When bacteria and other living cells grow and divide they pass through a series of stages in the life cycle marked by the occurrence of definite events; duplication of the chromosomes, growth in size, synthesis of particular enzymes, construction of cell septa, and cell division. Control mechanisms must operate in each cell to time correctly the turning on and off of the genes which contain the information for each process so that the cell reproduces itself accurately or does its proper job as part of a larger organism. These control mechanisms will be studied by following the synthesis and cell contents of DNA, RNA, protein, specific enzymes, special structures like ribosomes and cell walls and physiological variables like metal ion and nucleotide concentrations. Mutants unable to control the synthesis and concentration of these substances and structures will be sought as a means for studying the nature of each control process. Genes responsible for each control will be located on genetic maps and an attempt will be made to find patterns of organization of these maps related to the timing in the cell cycle and other relationships among the functions observed. These studies will be repeated for Escherichia coli, somatic mammalian cells and possibly other organisms in order to explore similarities and differences among species according to the evolutionary niche and biological function they serve. Virtually all of the usual techniques of modern molecular biology will be necessary for this work including the use of radioactive tracers, centrifugation, ultra- centrifugation, chromotography, electrophoresis, electron microscopy, and genetic recombination in addition to a large variety of purely chemical techniques. Continuous and batch culture methods will be used as necessary. Automated techniques for large scale quantitative observations on growing clones of cells will be exploited fully wherever possible. These techniques have been developed in our laboratories and are described in the accompanying proposal.